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Biomedical subjects

M Di Pierro

Publications and source records attributed to M Di Pierro.

8 recordsLinked to original sources

Charmed-meson decay constants in three-flavor lattice QCD.

We present the first lattice QCD calculation with realistic sea quark content of the D+-meson decay constant f(D+). We use the MILC Collaboration's publicly available ensembles of lattice gauge fields, which have a quark sea with two flavors (up and down) much lighter than a third (strange). We obtain f(D+)=201+/-3+/-17 MeV, where the errors are statistical and a combination of systematic errors. We also obtain f(Ds)=249+/-3+/-16 MeV for the Ds meson.

Journal Article↗

High-precision lattice QCD confronts experiment.

The recently developed Symanzik-improved staggered-quark discretization allows unquenched lattice-QCD simulations with much smaller (and more realistic) quark masses than previously possible. To test this formalism, we compare experiment with a variety of nonperturbative calculations in QCD drawn from a restricted set of "gold-plated" quantities. We find agreement to within statistical and systematic errors of 3% or less. We discuss the implications for phenomenology and, in particular, for heavy-quark physics.

Journal Article↗

Zonula occludens toxin structure-function analysis. Identification of the fragment biologically active on tight junctions and of the zonulin receptor binding domain.

Zonula occludens toxin (Zot) is an enterotoxin elaborated by Vibrio cholerae that increases intestinal permeability by interacting with a mammalian cell receptor with subsequent activation of intracellular signaling leading to the disassembly of the intercellular tight junctions. Zot localizes in the bacterial outer membrane of V. cholerae with subsequent cleavage and secretion of a carboxyl-terminal fragment in the host intestinal milieu. To identify the Zot domain(s) directly involved in the protein permeating effect, several zot gene deletion mutants were constructed and tested for their biological activity in the Ussing chamber assay and their ability to bind to the target receptor on intestinal epithelial cell cultures. The Zot biologically active domain was localized toward the carboxyl terminus of the protein and coincided with the predicted cleavage product generated by V. cholerae. This domain shared a putative receptor-binding motif with zonulin, the Zot mammalian analogue involved in tight junction modulation. Amino acid comparison between the Zot active fragment and zonulin, combined with site-directed mutagenesis experiments, confirmed the presence of an octapeptide receptor-binding domain toward the amino terminus of the processed Zot.

Amino Acid Sequence↗

[Zonula occludens toxin: an innovative method of oral drugs delivery].

Conventional forms of administration of nonabsorbable drugs and peptides often rely on parenteral injection, because the intestinal epithelium represents a major barrier to the oral absorption of these therapeutical agents into the systemic circulation. Recently, a number of innovative drug-delivery approaches have been developed, including drug entrapment within small vesicles or the passage of the therapeutic molecules through the space between adjacent intestinal cells. This article reviews some of the most promising techniques currently available for oral delivery and their possible practical applications for the delivery of vaccines and drugs for the treatment of clinical conditions that require frequent, chronic parenteral administration.

Adjuvants, Immunologic↗

Reduced quality of life in patients with chronic hepatitis C: effects of interferon treatment.

BACKGROUND: Quality of life is an area of increasing interest in hepatology. Studies, so far, have assessed quality of life in patients with chronic virus C-related hepatitis in relation to antiviral therapy by means of generic questionnaires. AIM: To measure quality of life in chronic hepatitis patients without cirrhosis by means of the Nottingham Health Profile questionnaire, a measure of "distress" in comparison with the Medical Outcome Survey SF-36, an index of well-being. PATIENTS: A series of 126 outpatients with chronic hepatitis; 37 on and 89 not on active interferon treatment. METHODS: The two questionnaires were used in random order. Clinical and laboratory data were also collected. The final score of any domain of the two questionnaires, for any individual patient, was compared to age-adjusted normal values obtained in 2 random samples of Italian population. RESULTS: Patients showed a significant modification of 3 domains of Nottingham Health Profile (Energy, Social Isolation and Physical Mobility) and 6 domains of SF-36. In relation to interferon treatment, the Nottingham Health Profile questionnaire was able to detect differences in Energy, Physical Mobility and Pain, which were modified only in treated patients. SF-36 did not show any differences in relation to treatment. In addition, the Nottingham Health Profile demonstrated that treated patients had a lower prevalence of concern for family life, possibly due to expectations of treatment itself. CONCLUSIONS: Active interferon treatment causes considerable distress in chronic hepatitis C patients, adding to the perceived change in health status caused by liver disease.

Adult↗

Drinking habits of subjects with hepatitis C virus-related chronic liver disease: prevalence and effect on clinical, virological and pathological aspects.

Alcohol changes the progression of hepatitis C virus (HCV)-related chronic liver disease and may affect the outcome of interferon therapy. The ethanol intake of 245 patients with biopsy-proven chronic hepatitis C with or without cirrhosis, its interaction with laboratory and histological parameters common to alcohol and HCV-mediated liver damage, and its effects on therapy were evaluated. The results show that 60-70% of subjects regularly consumed alcohol (median intake >40 g/day in about 30%). Less than 50% stopped drinking after being diagnosed as having liver disease. Ethanol intake affected: fibrosis, especially in women, HCV RNA levels, which were significantly lower in abstainers than in drinkers (0.6 +/- 0.3 vs 6.9 +/- 5.9 Eq/ml x10(6); P < 0.01), and response to interferon therapy. The number of responders decreased as ethanol intake increased. There were less abstainers than drinkers among non-responders (10.7% vs 63.1% respectively; P < 0.001). Data indicate that alcohol will induce and worsen liver damage and, in subjects with chronic liver disease who continue to drink, adversely affect their response to treatment.

Adult↗

The role of glutathione in the gastrointestinal tract: a review.

The primary role of glutathione is to protect cells from oxidative stress. It is abundantly distributed in the mucosal cells of gastrointestinal tract both in animals and man. The highest concentration is found in the duodenum. The amount of glutathione ingested with foods, age and drug or ethanol consumption affect glutathione concentration. The detoxifying capability of glutathione is directly related to its thiol group and to its function as a substrate for enzymatic activity; in fact, glutathione regulates the action of glutathione-peroxidases and glutathione-transferases. It has been documented that a direct relation between glutathione concentration and mucosal damage or between glutathione-related enzymes and cancer occurrence is present in various pathological conditions of the gastrointestinal tract (from oesophagus to rectum). The present review underlines: a) the role of oxidative stress in numerous physiological and pathological conditions in experimental animals and man; b) the need to maintain a normal antioxidant potential in the mucosal cells of the gastrointestinal tract; and c) the possibility to evaluate, through clinical studies, how glutathione concentration, food intake, and gastrointestinal diseases are associated.

Animals↗

[Steinert disease: abnormal onset or "casual" diagnosis?].

The most frequent myopathy is "Steinert's disease" (also called myotonic dystrophy). We present a case of particular interest due to the way diagnosis was made. A 20-year-old male was transferred to our Department from another Hospital with a diagnosis of "acute liver disease". He presented with fever (39 degrees C), tetrahyposthenia, dehydration and spatial-temporal disorientation. The most apparent laboratory data was a significant increase in serum levels of creatine phosphokinase (196,260 IU/L; normal values < 50 IU/L). After therapy based on parenteral nutrition and steroids, our patient improved progressively, with normalization of laboratory values. Muscle biopsy and electromyography yielded a diagnosis of Steinert's disease, and the patient's mother was found to be the carrier of a myotonine-kinase gene mutation. In this case, the onset of what appeared to be an influenza-A virus infection (the only positive data observed in the serological analysis) permitted the diagnosis of a hereditary myopathy that had remained asymptomatic up to that time.

Adult↗